Molecular mechanisms regulating the expression of class II histocompatibility molecules on macrophages. Effects of inductive and suppressive signals on gene transcription

The surface expression of class II MHC molecules (immune associated or Ia Ag) is an acquired and important property of macrophages. Recent evidence from several laboratories demonstrates that mRNA levels for class II genes reflect levels of surface expression. We have investigated the effects of agents that regulate Ia expression, either positively as IFN-gamma or negatively as bacterial LPS or maleylated proteins, on transcription of these genes. By using probes for I-A beta and I-E beta as representative class II MHC genes, we found that IFN-gamma induces transcription in murine peritoneal macrophages of I-A beta and of I-E beta as determined in nuclear run-on assays. The measured transcription peaked 6 to 10 h after administration of IFN-gamma to the macrophages. This augmented expression of transcription was markedly suppressed by administration of either LPS or maleylated protein to the macrophages. Collectively, the data indicate that regulation of transcription by either positive or negative stimuli, acting through surface receptors and binding sites, is a major mechanism for controlling the expression of class II MHC molecules in macrophages.